Acute Modulation of Stereotyped High Frequency Oscillations with a Closed-Loop Brain Interchange System in Drug Resistant Epilepsy

项目摘要： 颅内脑电（iEEG）的高频振荡（HFO）具有识别手术切除的潜力 区域/癫痫发作区（SOZ）。然而，多份报告显示， HFO不仅可以由癫痫脑组织产生，也可以由非癫痫部位产生，通常包括 运动、视觉和语言皮层等功能区。在这个项目中，我们提出了初步的证据， 可能足以区分病理性HFO与生理性HFO的复发性波形模式。 具体来说，我们表明，SOZ重复生成具有类似 波形形态，而从SOZ外记录的事件是不规则的。该形态 模式作为一种强大的神经生物标志物，将SOZ从多名患者的其他脑区中分离出来 始终如一虽然这些有希望的初步结果已经到位，但陈规定型观念的功能效用仍然存在。 闭环癫痫控制系统中的HFO仍然未知。 到目前为止，还不太清楚SOZ产生的定型HFO是否可以用一种 可植入系统。如果能够实现这一点，那么HFO可以战略性地转化为神经生物标志物， 闭环癫痫控制应用。我们假设病理定型的HFO可以被捕获 使用CorTec的植入式脑交换（BIC）系统，这些事件的空间拓扑可以 由可植入系统用来递送靶向电刺激以实现癫痫控制。使用 急性设置内癫痫监测单位（EMU），本项目将探讨捕获的可行性 使用新的BIC系统检测定型HFO事件，并将检测结果与使用 市场上可买到的放大器。如果我们研究的第一阶段（Aim-1）取得成功， 第二阶段（Aim-2），再次在EMU中，我们将向这些大脑部位提供有针对性的电刺激 与使用BIC的定型HFO相关。我们将研究这个闭环的调节作用 刺激策略，通过监测特征事件的变化，例如尖峰、癫痫放电、波纹 和快速的涟漪 如果成功的话，这个闭环系统不必等待癫痫发作开始才能提供刺激 在其开始时由Neuropace的RNS系统完成。相比之下，该系统将监测空间地形 和定型HFO的比率，并向这些区域提供有针对性的刺激，以防止癫痫发作。 如果我们在急性环境中的研究结果取得成功，我们将进行临床试验， 方法在慢性非卧床环境中植入BIC系统。 1

Project Summary: High frequency oscillations (HFOs) of intracranial EEG (iEEG) have the potential to identify the surgical resection area/seizure onset zone (SOZ) in patients with drug resistant epilepsy. However, multiple reports indicate that HFOs can be generated not only by epileptic cerebral tissue but also by non-epileptic sites often including eloquent regions such as motor, visual and language cortices. In this project, we present the initial evidence of a recurrent waveform pattern that may be sufficient to distinguish pathological HFOs from physiological ones. Specifically, we show that the SOZ repeatedly generates sets of stereotypical HFOs with similar waveform morphology whereas the events recorded from out of SOZ were irregular. This morphological pattern served as a robust neurobiomarker to isolate SOZ from other brain areas in multiple patients consistently. While these promising preliminary results are in place, the functional utility of stereotyped HFOs in a closed-loop seizure control system remains unknown. As of today, not much is known whether the stereotyped HFOs generated by the SOZ can be detected with an implantable system. If this can be achieved, then HFOs can be strategically translated as a neurobiomarker into closed-loop seizure control applications. We hypothesize that pathologic stereotyped HFOs can be captured with the implantable Brain Interchange (BIC) system of CorTec and spatial topography of these events can be utilized by the implantable system to deliver targeted electrical stimulation to achieve seizure control. Using an acute setup within the epilepsy monitoring unit (EMU), this project will investigate the feasibility of capturing stereotyped HFO events using the new BIC system and compare the detection results to those obtained with the commercially available amplifier. If the first phase (Aim-1) of our study becomes successful, later in the second phase (Aim-2), once again in the EMU, we will deliver targeted electrical stimulation to those brain sites associated with stereotyped HFOs using the BIC. We will investigate the modulatory effects of this closed-loop stimulation strategy by monitoring the changes in signature events such as spikes, epileptic discharges, ripples and fast ripples. If successful, this closed-loop system does not have to wait for a seizure to start in order to deliver the stimulation at its onset as done by the RNS system of Neuropace. In contrast, the system will monitor the spatial topography and rate of stereotyped HFOs and deliver targeted stimulation to these areas to prevent seizures from occurring. If the outcomes of our research in acute setting become successful, we will execute a clinical trial and run our methods with the implanted BIC system in a chronic ambulatory setting. 1